A novel potentiometric sensor based on ZnO decorated polyaniline/coal nanocomposite for diltiazem determination.

Diltiazem (DTZ) is one of the most effective medications for treating cardiovascular diseases. It has been widely used for the treatment of angina pectoris, hypertension and some types of arrhythmia. The development and application of a modified carbon paste sensor with improved detection limits for the potentiometric determination of diltiazem are the main goals of the current study. Sensitivity, long-term stability, reproducibility and improving the electrochemical performance are among the characteristics that have undergone careful examination. A modified carbon paste sensor based on ß-cyclodextrin (ß-CD) as ionophore, a lipophilic anionic additive (NaTPB) and a ZnO-decorated polyaniline/coal nanocomposite (ZnO@PANI/C) dissolved in dibutyl phthalate plasticizer, exhibited the best performance and Nernstian slope. The ZnO@PANI/C based sensor succeeded in lowering the detection limit to 5.0 × 10-7 through the linear range 1.0 × 10-6 to 1.0 × 10-2 mol L-1 with fast response time ≤ 10.0 s. The prepared nanomaterial was characterized using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). The surface properties of the proposed sensor were characterized by electrochemical impedance spectroscopy (EIS). The selectivity behavior of the investigated sensor was tested against a drug with similar chemical structure and biologically important blood electrolytes (Na+, K+, Mg2+, and Ca2+). The proposed analytical method was applied for DTZ analysis in pure drug, pharmaceutical products and industrial water samples with excellent recovery data.

Green and white MEKC for determination of different anti-diabetic binary mixtures and their triple-combo pill.

The work introduces green and white sustainable micellar electrokinetic chromatography (MEKC) procedure that could analyze therapeutically related drugs, empagliflozin (EMP), linagliptin (LIN) and metformin (MET) which are antidiabetic drugs with different mechanism of action, in their different pharmaceutical combinations. The method not only comply with the green analytical concepts, but also it is in line with sustainable analytical concepts as it is economic by applying the same operating conditions to analyze different pharmaceuticals in quality control (QC) labs which is a crucial step in QC labs and research centers to save time, effort, and money. Moreover, the method functionality regarding its scope with its achieved levels of accuracy, precision, low detection, and quantitation limits is tested using white assessment tool and compared with reported methods. The proposed MEKC coupled with a diode array detector (DAD) has been developed and validated for micro estimation of EMP and LIN in their low critical concentrations with MET in a ratio of (EMP: MET, 1:40) and (LIN: MET, 1:200). Separation was achieved within 6 min using fused silica capillary (40 cm × 50 µm id) using 20 mM Tris buffer (pH 10) in presence of 50 mM sodium dodecyl sulphate and 10% v/v methanol. The concentration ranges of the studied anti-diabetic drugs were 10-500, 10-100 and 2.5-100 µg. mL-1 for MET, EMP and LIN, respectively. The developed method is the first MEKC for concurrent determination of EMP, LIN and MET with high separation efficiency, low solvent consumption and regard as an easy green and white analytical tool. Moreover, Greenness and whiteness assessment were done via the most widely used Analytical Eco-Scale, the innovative AGREE tool and the RGB 12 algorithm.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. PATIENTS AND METHODS: Our study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. RESULTS: The sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. CONCLUSION: Ombitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.

Computational, in vitro and radiation-based in vivo studies on acetamide quinazolinone derivatives as new proposed purine nucleoside phosphorylase inhibitors for breast cancer.

The present work describes a quinazolinone-based lead optimization for the development of novel purine nucleoside phosphorylase (PNP) inhibitors with quinazolinone scaffold. Nineteen compounds were proposed and docked against PNP, the best 14 compounds with highest docking and affinity scores and low RMSD values were synthesized. Synthesis of new quinazolinone derivatives with variable acetamide substituents on two positions on quinazoline ring was performed. The structures assigned to the products were concordant with the microanalytical and spectral data. In vitro cytotoxicity on human breast cancer cell line (MCF7) was performed and identified compound 6g as the most potent with IC50 (0.99 ± 0.11 µM) which was further tested against five different breast cancer cell lines in addition to normal breast cell to determine the selectivity. Compound 6g was subjected to molecular dynamic simulation study, radiolabelling and biodistribution study to investigate its stability and selectivity toward breast cancers. The in vitro PNP inhibition results were aligned with the in silico, cytotoxicity, and biodistribution results where 6g showed the most potent PNP inhibitory activity with IC50 (0.159 ± 0.007 µM) when compared to Peldesine (BCX-34) IC50 (0.041 ± 0.002 µM).

Analysis of the Fragmentation Pathways for the Collision-Induced Dissociation of Protonated Cyclophosphamide: A Mass Spectrometry and Quantum Mechanical Study.

Cyclophosphamide is a well-known anticancer agent acting by means of DNA alkylation. Associated with its tumor selectivity, it also possesses a wide spectrum of toxicities. As the requirement of metabolic activation before cyclophosphamide exerts either its therapeutic or toxic effects is well recognized, research aiming at elucidating the pathways that lead to the activation of this drug is of key importance. This has created the necessity for developing an effective analytical method for detecting cyclophosphamide and its breakdown products. In this paper, an Acquity TQ tandem quadrupole mass spectrometer equipped with electrospray ionization in positive-ion mode was employed for detecting cyclophosphamide in its protonated form. The full-scan mass spectrum of cyclophosphamide shows two ion clusters displaying the characteristic isotopic pattern of two chlorine atoms and assigned as sodiated cyclophosphamide, [CP + Na]+, and protonated cyclophosphamide, [CP + H]+ or PCP. With the aid of quantum mechanical DFT calculation, free energy differences in the gas phase among PCP protomers were computed with respect to the most stable protomer being protonated on the 2-oxide oxygen of the 1,3,2-oxazaphosphorine-2-oxide ring. In addition, the interconversion mechanisms among the different protomers were also proposed by intercepting the corresponding transition states in the gas phase. Collision-induced dissociation (CID) of PCP generated six characteristic product ions. Fragmentation mechanisms were proposed and supported by computation. The calculated energy barriers for all of the located transition states were found to be accessible under the reported experimental conditions.

In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS.

The use of complementary medicine (CMD) for liver support in Hepatitis C virus (HCV) patients sometimes coincides with the administration of oral antiviral drugs to eradicate the virus. This calls for a deep investigation of CMD effects on the pharmacokinetic parameters of these drugs to ensure their safety and efficacy. Silymarin (SLY), as a CMD, was selected to be given orally to healthy male rats with sofosbuvir (SFB) and ledipasvir (LED), a common regimen in HCV treatment. A new and sensitive LC-MS method was validated for the bioassay of SLY, LED, SFB and its inactive metabolite, GS-331007, in spiked plasma with lower limits of quantitation of 10, 1, 4 and 10 ng/ml, respectively. Moreover, the method was further applied to conduct a full pharmacokinetic profile of SFB, GS-331007 and ledipasvir with and without SLY. It was found that co-administration of SLY may expose the patient to unplanned high serum concentrations of SFB and LED. This could be accompanied by a decrease in SFB efficacy, potentially leading to therapeutic failure and the emergence of viral resistance.

HPLC/Fluorescence-Diode Array Detection for Rapid and Reliable Determination of Illegal Synthetic Drugs in Male Sexual Herbal and Honey Remedies: Comparative Study with UFLC-MS.

BACKGROUND: Nutraceuticals (NTCs), as honey and tablets with herbal extract are subjected to adulteration. OBJECTIVE: For NTCs claimed to enhance sexual performance, synthetic drugs (sildenafil, tadalafil, avanafil, vardenafil, and dapoxetine) are common adulterants, so they were selected to be simultaneously analyzed in the current study. Natural aphrodisiacs (icariin and yohimbine) are claimed to be present in many fake NTCs, so they were also included in the study. METHODS: In order to achieve the target of the current study, three liquid chromatographic methods with different unique detectors were developed and validated. RESULTS: High performance liquid chromatography (HPLC) with fluorescence detection enables rapid and reliable determination of natively fluorescent yohimbine, tadalafil vardenafil, and dapoxetine and it is the first report to analyze these compounds as adulterants in counterfeit NTC. Although the diode-array detector (DAD) enables the analysis of the seven adulterants, the fluorescence detector (FLD) shows better sensitivity and selectivity with lower LOQs and LODs. On the other hand, ultra-fast liquid chromatography-mass spectrometry (UFLC-MS) offers the advantages of peak identity confirmation, and it is of comparable sensitivity and selectivity to HPLC-FLD. CONCLUSION: One or more of these synthetic drugs were found in the analyzed NTCs while natural aphrodisiacs were absent. HIGHLIGHTS: Aphrodisiac nutraceuticals, NTCs, were analyzed for adulterants: five aphrodisiac synthetic drugs (adulterants) and two natural claimed aphrodisiacs. UFLC-MS and HPLC-DAD/FLD were compared for illicit NTCs analysis; all NTCs show the presence of synthetic aphrodisiacs and the absence of natural ones.

Stability-indicating RP-HPLC assay of three novel oral anticoagulants binary mixtures with rosuvastatin calcium: Application to pharmaceutical preparations and human plasma.

The binary mixtures of the novel oral anticoagulants (NOACs); Apixaban (APX), Edoxaban tosylate (EDX) and Rivaroxaban (RIV) with the lipid lowering statin; Rosuvastatin calcium were analyzed using a validated HPLC-DAD method. This method was suitable for the quantitative assay of the targeted mixtures in tablets and human plasma. The analysis in dosage form was a stability indicating one where the drugs were separated from possible degradation products arising from applying different stress conditions. For analysis in human plasma, EDX was used as internal standard in APX/ROS and RIV/ROS mixtures, while APX was used as internal standard in EDX/ROS mixture and the method was validated according to FDA regulation for analysis in biological fluids. A ZORBAX Eclipse column C18 (4.6 × 150 mm × 5 µm) was used as stationary phase with a gradient eluting mobile phase composed of acidified water and acetonitrile. The method selectivity was demonstrated by its ability to simultaneously analyze the drugs in presence of possible forced degradation products and dosage form excipients and in presence of plasma interferences (analysis in biological fluid) at a single wavelength (291 nm) with the use of the internal standard. The simplicity of the method emphasizes its capability to analyze the drugs in pharmaceutical preparations and human plasma. This is very important in regular clinical monitoring of the drugs plasma concentrations for cardiovascular patients medicated with either of these combinations, as prophylaxis from stroke, in order to prevent severe bleeding and to achieve optimum dose adjustment.

A Review on Analytical Strategies for the Assessment of Recently Approved Direct Acting Antiviral Drugs.

Human beings are in dire need of developing an efficient treatment against fierce viruses like hepatitis C virus (HCV) and Coronavirus (COVID-19). These viruses have already caused the death of over two million people all over the world. Therefore, over the last years, many direct-acting antiviral drugs (DAADs) were developed targeting nonstructural proteins of these two viruses. Among these DAADs, several drugs were found more effective and safer than the others as sofosbuvir, ledipasvir, grazoprevir, glecaprevir, voxilaprevir, velpatasvir, elbasvir, pibrentasvir and remdesivir. The last one is indicated for COVID-19, while the rest are indicated for HCV treatment. Due to the valuable impact of these DAADs, larger number of analytical methods were required to meet the needs of the clinical studies. Therefore, this review will highlight the current approaches, published in the period between 2017 to present, dealing with the determination of these drugs in two different matrices: pharmaceuticals and biological fluids with the challenges of analyzing these drugs either alone, with other drugs, in presence of interferences (pharmaceutical excipients or endogenous plasma components) or in presence of matrix impurities, degradation products and metabolites. These approaches include spectroscopic, chromatographic, capillary electrophoretic, voltametric and nuclear magnetic resonance methods that have been reported during this period. Moreover, the analytical instrumentation and methods used in determination of these DAADs will be illustrated in tabulated forms.

HPLC with fluorescence detection for the bioanalysis and pharmacokinetic study of Doxorubicin and Prodigiosin loaded on eco-friendly casein nanomicelles in rat plasma.

A rapid, efficient, and sensitive liquid chromatographic assay hyphenated to fluorometric detector (HPLC-FLD) was developed and validated for the determination of doxorubicin (DXR) and prodigiosin (PDG) in rat plasma. The sample pre-treatment involves a protein precipitation with acetonitrile with satisfying extraction efficiency (98% and 85% for DXR and PDG, respectively). The chromatographic separation was accomplished using stationary phase: Agilent Zorbax Eclipse plus-C18 analytical column (250 × 4.6 mm, 5 µm) and gradient eluting mobile phase of ammonium acetate (pH = 3), acetonitrile and methanol with programmed fluorescence detection. As the proposed method has been validated, it was subsequently implemented to evaluate DXR and PDG loaded on novel eco-friendly Casein nano drug delivery system after intravenous injection in healthy rats. A comparative pharmacokinetics' study was carried out in rats for DXR in free form, DXR alone entrapped in the nanomicelle and DXR with PDG entrapped in the nano micelle. After testing the differences in pharmacokinetic parameters of the different formulations using ANOVA, the results showed insignificant differences among the tested parameters. This indicates that the presented nanomicelle delivery system has succeeded to incorporate PDG and DXR in a hydrophilic, safe, and potent formulation. This novel nanomicelle has negligible effect on the distribution and elimination of DXR.

Exhibiting the diagnostic face of selenium nanoparticles as a radio-platform for tumor imaging.

Selenium nanoparticles (SeNPs) have become one of the most prospective and promising tools in the course of cancer diagnosis and therapy. Here we describe the synthesis of a novel radioactive platform for tumor imaging using selenium nanoparticles. SeNPs were synthetized using dithionite and glutathione as reducing and capping agent respectively with 5 mmol/L sodium selenite as a precursor and then SeNPs radiolabeled with technetium-99 m, the most common and famous radioactive isotope used for imaging purposes. A characteristic profile for the synthesized SeNPs was performed including size analysis, zeta potential, antioxidant activity, radiochemical yield and in-vivo biodistribution in normal and solid tumor bearing mice. Size analysis showed amorphous SeNP cores of a mean diameter of 21 ± 5 nm with a hydrodynamic size of 43 ± 8 nm and -28 mV zeta potential. The particles also showed a superior antioxidant activity of radical scavenging activity 55.6% according to DPPH assay, in addition, satisfying radiochemical yield up to 97 ± 1.5 was achieved. In vivo studies were applied on male Swiss albino mice that demonstrated a good biodistribution pattern in normal mice with a moderate accumulation in liver at 30 min post injection. Excellent T/NT ratios were obtained in solid tumor bearing mice throughout the experimental time points. The as-synthetized selenium nanoparticles demonstrated surprising and satisfying features which make them promising enough for tumor theranosis.

A Validated Stability-Indicating HPTLC Assay for Determination of 10-Hydroxy-2-Decenoic Acid Content in Royal Jelly Products Using Robust Regression Methods.

A new, simple, stability-indicating high-performance thin-layer chromatography method was developed for the quantification of 10-hydroxy-2-decenoic acid (10-HDA) in some royal jelly products marketed in Egypt. The used solvent system was chloroform:acetic acid (10:1, v/v) and the bands were measured densitometrically at 210 nm. First- and second-derivative treatments of the data were performed. The present study shows a comparison between three statistical regression methods for handling data: parametric, nonparametric and weighted regression (WR) methods. The developed methods were validated as per International Conference on Harmonization guidelines. To validate the stability-indicating power of the developed analytical method, the royal jelly standard was subjected to forced degradation studies including the effect of hydrolysis, oxidation, photolysis and dry heat. It was found that derivative treatment of the chromatographic response data gives improved quantitation and sensitivity of the chromatographic signals. Weighted regression of the response data is found to be advantageous over the use of both parametric and nonparametric regression models. This was shown by a great enhancement in the accuracy and precision in the analysis of 10-HDA in royal jelly products. The % recovery in case of WR was 99.92 ± 0.16, while % recovery in case of nonparametric and parametric regressions were 99.56 ± 0.25 and 98.63 ± 0.65, respectively.

Analysis of astragalosides I, II and IV in some Egyptian Astragalus species and Astragalus dietary supplements using high-performance liquid chromatography/evaporative light scattering detector and non-parametric regression.

INTRODUCTION: GenuTs Astragalus L. is characterised by the presence of cycloartane saponins which have wide biological activities such as antioxidant, immunomodulating' hepatoprotective and anti-inflammatory activities. From these cycloartane saponins are astragalosides I, II and IV which have been regarded as the most important active constituents in Astragalus species. OBJECTIVES: This work describes the quantitative analysis of astragalosides I, II and IV in some Egyptian Astragalus species and Astragalus dietary supplements in a single run by high-performance liquid chromatography/evaporative light scattering detector (HPLC/ELSD) using gradient elution. METHODOLOGY: The method of quantitation adopted in this study is the standard addition method. First and second derivative treatment of the data was performed, and the study presents comparison between two statistical regression methods for handling data; parametric and non-parametric regression methods. RESULTS: Derivative treatment of the chromatographic response data gives improved quantitation of the chromatographic signals. Non-parametric regression of the data using Theil's method is advantageous over the usual least squares method as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points. CONCLUSION: Due to the simplicity and the good accuracy and reproducibility of the suggested methods, they could be used for analysis and quality control of Astragalus species and Astragalus dietary supplements.

Potentiometric sensor based on novel flowered-like Mg-Al layered double hydroxides/multiwalled carbon nanotubes nanocomposite for bambuterol hydrochloride determination.

Nowadays, development of highly efficient potentiometric sensors attracts the attention of many researchers over the world; due to the great expansion of portable analytical devices. This study aims to apply a current development to the construction and sense of carbon paste sensors based on flowered-like Mg-Al layered double hydroxides/multiwalled carbon nanotubes (FLLDH/MWCNTs) (sensor І), FLLDH/titanate nanotubes (TNTs) (sensor ІІ) and MWCNTs/TNTs (sensor ІІІ) nanocomposites for bambuterol hydrochloride analysis; to enhance the potentiometric response towards determination of the drug. The sensors exhibited excellent Nernstian slopes 58.8 ±â€¯0.5, 58.5 ±â€¯0.8 and 57.4 ±â€¯0.7 mV/decade with linear working ranges of 1.0 × 10-7-1.0 × 10-2, 1.0 × 10-6-1.0 × 10-2 and 1.0 × 10-7-1.0 × 10-2 mol L-1, detection limits 2.3 × 10-8, 2.5 × 10-7and 7.5 × 10-8 mol L-1 and quantification limits of 7.6 × 10-8, 8.3 × 10-7and 2.5 × 10-7 mol L-1 for sensor І, ІІ and ІІІ, respectively. The selectivity behaviour of the investigated sensors was tested against biologically important blood electrolytes (Na+, K+, Mg2+, Ca2+). The proposed analytical method was successfully applied for BAM determination in pure drug, pharmaceutical products, surface water, human plasma and urine samples with excellent recovery data (99.62, 99.10 and 98.95%) for the three sensors, respectively.

Voltammetric analysis of dantrolene and its active metabolite with indomethacin in rat plasma.

AIM: Differential pulse polarography was used for the concurrent analysis of the coadministered dantrolene (DAN) and indomethacin (IND) in plasma. MATERIALS & METHODS: DAN and IND, Hanging mercury drop electrode and Britton-Robinson buffer at pH 5 were used. In plasma, cathodic reduction of DAN nitro group and its active metabolite at -0.2 V was done. IND was analyzed after carbonyl group reduction at -1.1 V. RESULTS: Drugs determination in rat plasma with good recoveries and low limit of quantitation was done. Application to trace analysis of drugs in rat plasma was done with Cmax and Tmax determination. CONCLUSION: This technique shows high sensitivity, simplicity and low cost. The method is US FDA validated and it is applicable to human level.

Chemometrics-assisted spectrophotometric green method for correcting interferences in biowaiver studies: Application to assay and dissolution profiling study of donepezil hydrochloride tablets.

A green, simple and cost effective chemometric UV-Vis spectrophotometric method has been developed and validated for correcting interferences that arise during conducting biowaiver studies. Chemometric manipulation has been done for enhancing the results of direct absorbance, resulting from very low concentrations (high incidence of background noise interference) of earlier points in the dissolution timing in case of dissolution profile using first and second derivative (D1 & D2) methods and their corresponding Fourier function convoluted methods (D1/FF& D2/FF). The method applied for biowaiver study of Donepezil Hydrochloride (DH) as a representative model was done by comparing two different dosage forms containing 5mg DH per tablet as an application of a developed chemometric method for correcting interferences as well as for the assay and dissolution testing in its tablet dosage form. The results showed that first derivative technique can be used for enhancement of the data in case of low concentration range of DH (1-8µgmL-1) in the three different pH dissolution media which were used to estimate the low drug concentrations dissolved at the early points in the biowaiver study. Furthermore, the results showed similarity in phosphate buffer pH6.8 and dissimilarity in the other 2pH media. The method was validated according to ICH guidelines and USP monograph for both assays (HCl of pH1.2) and dissolution study in 3pH media (HCl of pH1.2, acetate buffer of pH4.5 and phosphate buffer of pH6.8). Finally, the assessment of the method greenness was done using two different assessment techniques: National Environmental Method Index label and Eco scale methods. Both techniques ascertained the greenness of the proposed method.

High performance thin-layer and high performance liquid chromatography coupled with photodiode array and fluorescence detectors for analysis of valsartan and sacubitril in their supramolecular complex with quantitation of sacubitril-related substance in raw material and tablets.

Valsartan (VAL) and sacubitril (SAC) are combined in a supramolecular complex, LCZ696, which is a newly approved remedy for heart failure. SAC-related substance (biphenyl methyl pyrrolidinone [BMP]) which also appears as an intermediate during SAC synthesis is considered to be a suspected impurity for SAC and/or LCZ696 tablets. The study investigates the analysis of VAL and SAC in their supramolecular complex along with SAC-related substance, BMP, using high performance thin-layer chromatography (HPTLC) and high performance liquid chromatography (HPLC) with two different detectors; fluorescence detector (FLD) and diode array detector (DAD). The work aimed at analyzing BMP at low levels in the presence of its parent drug, SAC. BMP was successfully analyzed at a level of 0.167, 1 and 3% of its parent drug, SAC upon using HPLC-FLD, HPLC-DAD and HPTLC, respectively. For HPLC-FLD, the detector was set at λex/λem (nm/nm): 0-4.5 min at 255/374; 4.5-6 min at 255/314, for achieving an adequate sensitivity of the method to monitor and quantify VAL and SAC in the presence of BMP. Low limits of detection (8.3, 3.3 and 1.7 ng mL-1) and limits of quantitation (25, 10 and 5 ng mL-1) values obtained for VAL, SAC and BMP, respectively, upon using FLD suggest that low level of baseline noise enables the detection and quantitation of low BMP concentration.

Least median of squares and iteratively re-weighted least squares as robust linear regression methods for fluorimetric determination of α-lipoic acid in capsules in ideal and non-ideal cases of linearity.

This study outlines two robust regression approaches, namely least median of squares (LMS) and iteratively re-weighted least squares (IRLS) to investigate their application in instrument analysis of nutraceuticals (that is, fluorescence quenching of merbromin reagent upon lipoic acid addition). These robust regression methods were used to calculate calibration data from the fluorescence quenching reaction (∆F and F-ratio) under ideal or non-ideal linearity conditions. For each condition, data were treated using three regression fittings: Ordinary Least Squares (OLS), LMS and IRLS. Assessment of linearity, limits of detection (LOD) and quantitation (LOQ), accuracy and precision were carefully studied for each condition. LMS and IRLS regression line fittings showed significant improvement in correlation coefficients and all regression parameters for both methods and both conditions. In the ideal linearity condition, the intercept and slope changed insignificantly, but a dramatic change was observed for the non-ideal condition and linearity intercept. Under both linearity conditions, LOD and LOQ values after the robust regression line fitting of data were lower than those obtained before data treatment. The results obtained after statistical treatment indicated that the linearity ranges for drug determination could be expanded to lower limits of quantitation by enhancing the regression equation parameters after data treatment. Analysis results for lipoic acid in capsules, using both fluorimetric methods, treated by parametric OLS and after treatment by robust LMS and IRLS were compared for both linearity conditions.

Green gas chromatographic stability-indicating method for the determination of Lacosamide in tablets. Application to in-vivo human urine profiling.

A direct, eco-friendly, stability-indicating GC method was developed for the determination of Lacosamide (LCM) in tablet dosage forms in presence of its degradation products as well as in human urine in presence of the co-administered drug Zonisamide (ZON). The assay method in tablets was validated according to the ICH guidelines, while the method for determination of LCM in urine was validated according to FDA; Bioanalytical Method Validation guidance. Linear response (r = 0.9998) was observed over the range of 20-280 µg/mL of LCM, with detection and quantitation limits of 5.871 and 19.57 µg/mL, respectively for the tablet assay method. While (r = 0.9999) was observed over the range of 0.5-20 µg/mL of LCM, with detection and quantitation limits of 67 and 233 ng mL-1, respectively for the urine analysis method. Under various stress conditions, the investigation of LCM forced degradation behaviour was carried out. Furthermore, monitoring of the drug in urine followed by construction of its urine profile was done after the administration of 50 mg tablet of LCM to three healthy volunteers so as to prove the ability of the method to be applied in assaying LCM in human urine. The method showed also successful separation of LCM and the co-administered drug ZON in urine. Finally, the greenness of the method was assessed using National Environmental Methods Index label and Eco scale methods.

Spur-of-the-Moment Modification in National Treatment Policies Leads to a Surprising HCV Viral Suppression in All Treated Patients: Real-Life Egyptian Experience.

The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming. All group 1 patients (1,214 patients) achieved SVR12 (100%) and this was statistically significant when compared with the overall SVR12 in group 2 [8,869 patients with sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse events were reported in both groups. In this real-life treatment experience, interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV viral suppression in all treated patients.